The specific aims of the parent grant are to describe the clinical manifestations of Lyme Disease in patients in New England, to develop specific diagnostic tests, and to determine appropriate treatment regimens for the illness. Since 1986, Dr. Steere, the Principal Investigator of the parent grant, has participated in a cooperative exchange with physicians at the Rheumatology Institute in Moscow under the auspices of the U.S.-U.S.S.R. Biological Health Agreement. It is now known that a considerable portion of the worldwide nosoarea of Lyme borreliosis is situated within the former Soviet Union. The infection there may be caused by any of the three currently identified groups of the B. burgdorferi sensu latu complex, including B. burgdorferi sensu stricto, B. garinii, and B. afzelii. However, the characteristics of the disease, particularly the late manifestations of the illness, are incompletely described in Russia, and for the most part, accurate diagnostic testing is not yet available there. In the proposed study, the clinical manifestations of Lyme borreliosis in Russian patients will be described based on a referral network of patients seen at the Rheumatology and Neurology Institutes in Moscow, and patients seen at the Lyme Disease Center at Ekaterinburg, a highly endemic area in the Ural Mountains, about 1,000 miles east of Moscow. A Lyme disease diagnostic laboratory will be developed in Moscow, and sensitive and specific diagnostic criteria for ELISA and Western blotting tests will be developed, based on Russian case and control subjects. Skin biopsy samples of erythema migrans skin lesions will be cultured, and joint fluid and cerebrospinal fluid samples will be tested by PCR in an effort to identify the groups of the B. borrelia burgdorferi sensu latu complex which cause this infection in Russia. Finally, the clinical data will be correlated with the laboratory information in an attempt to determine whether particular spirochetal groups cause different clinical pictures with different serologic responses in Russia. These studies are important both to understand variations of this infection in different parts of the world and to aid in the diagnosis and treatment of Russian patients with this curable infection.